Advances in Diagnosis and Treatment of Heart Failure by Intestinal Microbiota

doi:10.12114/j.issn.1007-9572.2019.00.306

Abstract

Abstract: The physiological role of intestinal microbiota in non-gastrointestinal diseases has attracted growing attention of researchers, which has also been shown to be an important factor in the pathogenesis and development of heart failure.There are characteristic changes in intestinal microbiota composition in patients with heart failure, such as the increase of harmful microbiota and their metabolites, for example trimethylamine oxide（TMAO）, and the decrease of protective microbiota and their metabolites, for example short-chain fatty acids. Meanwhile, heart failure can also induce intestinal congestion, edema, and heightened permeability, allowing harmful microbiota and their toxic metabolites such as endotoxin into the circulation through the intestinal wall, which triggers cytokine generation and activates signal pathway, thereby contributing to further impairment in cardiac function. Given the importance of intestinal microbiota in the development of heart failure, it is expected that regulating intestinal microbiota and interfering with its metabolites will be a new target for the diagnosis and treatment of heart failure. The article aims to review the changes of intestinal microbial composition, the mechanism of their toxic metabolites in heart failure and the research progress in interventional intestinal microbiota in the treatment of heart failure.

Key words: Heart failure, Intestinal microbiota, Microbial metabolite, Pathogenesis, Therapy, Review

摘要： 肠道微生物在非胃肠疾病中发挥的重要生理作用逐渐引起医学界关注及重视，其亦被证实是影响心力衰竭发生、发展的重要因素。心力衰竭患者的肠道微生物组成存在特征性改变，如有害性微生物及其代谢产物氧化三甲胺（TMAO）等增多、保护性微生物及其代谢产物短链脂肪酸减少。同时，心力衰竭也可引起肠道淤血水肿、通透性增加，促使有害性微生物及其产生的内毒素、代谢产物经肠壁进入循环，从而刺激机体产生促炎性因子并通过调节相关信号通路进一步加重心力衰竭。鉴于肠道微生物在心力衰竭疾病发展过程中的重要作用，通过调节肠道微生物组成及干预其代谢产物有望成为心力衰竭诊疗的新靶点，本文将对心力衰竭时肠道微生物组成变化及其代谢产物在心力衰竭中的作用机制进行阐述，同时介绍通过干预肠道微生物治疗心力衰竭的研究进展。

关键词: 心力衰竭, 肠道微生物, 微生物代谢产物, 发病机制, 治疗, 综述

CHEN Zijun,ZHU Bin,YANG Chun, et al. Advances in Diagnosis and Treatment of Heart Failure by Intestinal Microbiota　[J]. Chinese General Practice, 2019, 22(35): 4346-4352. DOI: 10.12114/j.issn.1007-9572.2019.00.306.
陈子俊,朱滨,杨春等. 肠道微生物与心力衰竭诊治的研究进展[J]. 中国全科医学, 2019, 22(35): 4346-4352. DOI: 10.12114/j.issn.1007-9572.2019.00.306.

References

［1］SENDER R，FUCHS S，MILO R.Are we really vastly outnumbered？Revisiting the ratio of bacterial to host cells in humans［J］．Cell，2016，164（3）：337-340．DOI：10.1016/j.cell.2016.01.013.
［2］NICHOLSON J K，HOLMES E，KINROSS J，et al．Host-gut microbiota metabolic interactions［J］．Science，2012，336（6086）：1262-1267．DOI：10.1126/science.1223813.
［3］LI M，WANG B H，ZHANG M H，et al．Symbiotic gut microbes modulate human metabolic phenotypes［J］．Proc Natl Acad Sci USA，2008，105（6）：2117-2122．DOI：10.1073/pnas.0712038105.
［4］ASKOXYLAKIS V，THIEKE C，PLEGER S T，et al．Long-term survival of cancer patients compared to heart failure and stroke：a systematic review［J］．BMC Cancer，2010，10（1）：105．DOI：10.1186/1471-2407-10-105.
［5］VON LUEDER T G，SANGARALINGHAM S J，WANG B H，et al．
Renin-angiotensin blockade combined with natriuretic peptide system augmentation：novel therapeutic concepts to combat heart failure［J］．Circ Heart Fail，2013，6（3）：594-605．DOI：10.1161/CIRCHEARTFAILURE.112.000289.
［6］NAGATOMO Y，TANG W H.Intersections between microbiome and heart failure：revisiting the gut hypothesis［J］．J Card Fail，2015，21（12）：973-980．DOI：10.1016/j.cardfail.2015.09.017.
［7］SANDEK A，BAUDITZ J，SWIDSINSKI A，et al．Altered intestinal function in patients with chronic heart failure［J］．J Am Coll Cardiol，2007，50（16）：1561-1569．DOI：10.1016/j.jacc.2007.07.016.
［8］CUI X，YE L，LI J，et al．Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients［J］．Sci Rep，2018，8（1）：635．DOI：10.1038/s41598-017-18756-2.
［9］KATSIMICHAS T，OHTANI T，MOTOOKA D，et al．Non-ischemic heart failure with reduced ejection fraction is associated with altered intestinal microbiota［J］．Circ J，2018，82（6）：1640-1650．DOI：10.1253/circj.CJ-17-1285.
［10］KAMO T，AKAZAWA H，SUDA W，et al．Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure［J］．PLoS One，2017，12（3）：e0174099．DOI：10.1371/journal.pone.0174099.
［11］LUEDDE M，WINKLER T，HEINSEN F A，et al．Heart failure is associated with depletion of core intestinal microbiota［J］．ESC Heart Fail，2017，4（3）：282-290．DOI：10.1002/ehf2.12155.
［12］KARLSSON F H，F?K F，NOOKAEW I，et al．Symptomatic atherosclerosis is associated with an altered gut metagenome［J］．Nat Commun，2012，3（6）：1245．DOI：10.1038/ncomms2266.
［13］LAMBETH S M，CARSON T，LOWE J，et al．Composition，diversity and abundance of gut microbiome in prediabetes and type 2 diabetes［J］．J Diabetes Obes，2015，2（3）：1-7．DOI：10.15436/2376-0949.15.031.
［14］KRACK A，RICHARTZ B M，GASTMANN A，et al．Studies on intragastric PCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure［J］．Eur J Heart Fail，2004，6（4）：403-407．DOI：10.1016/j.ejheart.2004.03.002.
［15］MUKHERJEE S，HOOPER L V.Antimicrobial defense of the intestine［J］．Immunity，2015，42（1）：28-39．DOI：10.1016/j.immuni.2014.12.028.
［16］KITAI T，KIRSOP J，TANG W H.Exploring the microbiome in heart failure［J］．Curr Heart Fail Rep，2016，13（2）：103-109．DOI：10.1007/s11897-016-0285-9.
［17］HOOPER L V，LITTMAN D R，MACPHERSON A J.Interactions between the microbiota and the immune system［J］．Science，2012，336（6086）：1268-1273．DOI：10.1126/science.1223490.
［18］SANDEK A，BJARNASON I，VOLK H D，et al．Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure［J］．Int J Cardiol，2012，157（1）：80-85．DOI：10.1016/j.ijcard.2010.12.016.
［19］MELéNDEZ G C，MCLARTY J L，LEVICK S P，et al．Interleukin 6 mediates myocardial fibrosis，concentric hypertrophy，and diastolic dysfunction in rats［J］．Hypertension，2010，56（2）：225-231．DOI：10.1161/HYPERTENSIONAHA.109.148635.
［20］DHINGRA S，BAGCHI A K，LUDKE A L，et al．Akt regulates IL-10 mediated suppression of TNFα-induced cardiomyocyte apoptosis by upregulating Stat3 phosphorylation［J］．PLoS One，2011，6（9）：e25009．DOI：10.1371/journal.pone.0025009.
［21］KUMMEN M，MAYERHOFER C C K，VESTAD B，et al．Gut microbiota signature in heart failure defined from profiling of 2 independent cohorts［J］．J Am Coll Cardiol，2018，71（10）：1184-1186．DOI：10.1016/j.jacc.2017.12.057.
［22］HOFFMANN T W，PHAM H P，BRIDONNEAU C，et al．Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice［J］．ISME J，2016，10（2）：460-477．DOI：10.1038/ismej.2015.127.
［23］MANN D L.Innate immunity and the failing heart：the cytokine hypothesis revisited［J］．Circ Res，2015，116（7）：1254-1268．DOI：10.1161/CIRCRESAHA.116.302317.
［24］SOKOL H，PIGNEUR B，WATTERLOT L，et al．Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients［J］．Proc Natl Acad Sci USA，2008，105（43）：16731-16736．DOI：10.1073/pnas.0804812105.
［25］LOUIS P，FLINT H J.Diversity，metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine［J］．FEMS Microbiol Lett，2009，294（1）：1-8．DOI：10.1111/j.1574-6968.2009.01514.x.
［26］BURKARD T，PFISTER O，RICKLI H，et al．Prognostic impact of systemic inflammatory diseases in elderly patients with congestive heart failure［J］．QJM，2014，107（2）：131-138．DOI：10.1093/qjmed/hct205.
［27］NIAN M，LEE P，KHAPER N，et al．Inflammatory cytokines and postmyocardial infarction remodeling［J］．Circ Res，2004，94（12）：1543-1553．DOI：10.1161/01.RES.0000130526.20854.fa.
［28］ZHANG F Y，XIA Y L，YAN W J，et al．Sphingosine 1-phosphate signaling contributes to cardiac inflammation，dysfunction，and remodeling following myocardial infarction［J］．Am J Physiol Heart Circ Physiol，2016，310（2）：H250-261．DOI：10.1152/ajpheart.00372.2015.
［29］TR?SEID M，UELAND T，HOV J R，et al．Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure［J］．J Intern Med，2015，277（6）：717-726．DOI：10.1111/joim.12328.
［30］JOHNSON C，PROKOPIENKO A J，WEST R E 3rd，et al．Decreased kidney function is associated with enhanced hepatic flavin monooxygenase activity and increased circulating trimethylamine n-oxide concentrations in mice［J］．Drug Metab Dispos，2018，46（9）：1304-1309．DOI：10.1124/dmd.118.081646.
［31］SAVI M，BOCCHI L，BRESCIANI L，et al．Trimethylamine-N-oxide（TMAO）-induced impairment of cardiomyocyte function and the protective role of urolithin B-glucuronide［J］．Molecules，2018，23（3）：E549．DOI：10.3390/molecules23030549.
［32］UFNAL M，JAZWIEC R，DADLEZ M，et al．Trimethylamine-N-oxide：a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats［J］．Can J Cardiol，2014，30（12）：1700-1705．DOI：10.1016/j.cjca.2014.09.010.
［33］ROBERTS A B，GU X D，BUFFA J A，et al．Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential［J］．Nat Med，2018，24（9）：1407-1417．DOI：10.1038/s41591-018-0128-1.
［34］ZHU W F，GREGORY J C，ORG E，et al．Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk［J］．Cell，2016，165（1）：111-124．DOI：10.1016/j.cell.2016.02.011.
［35］SUZUKI T，HEANEY L M，BHANDARI S S，et al．Trimethylamine N-oxide and prognosis in acute heart failure［J］．Heart，2016，102（11）：841-848．DOI：10.1136/heartjnl-2015-308826.
［36］SAVIRA F，MAGAYE R，HUA Y，et al．Molecular mechanisms of protein-bound uremic toxin-mediated cardiac，renal and vascular effects：underpinning intracellular targets for cardiorenal syndrome therapy［J］．Toxicol Lett，2019，308（12）：34-49．DOI：10.1016/j.toxlet.2019.03.002.
［37］LEKAWANVIJIT S，ADRAHTAS A，KELLY D J，et al．Does indoxyl sulfate，a uraemic toxin，have direct effects on cardiac fibroblasts and myocytes?［J］．Eur Heart J，2010，31（14）：1771-1779．DOI：10.1093/eurheartj/ehp574.
［38］YANG K，WANG C，NIE L，et al．Klotho protects against indoxyl sulphate-induced myocardial hypertrophy［J］．J Am Soc Nephrol，2015，26（10）：2434-2446．DOI：10.1681/ASN.2014060543.
［39］SAVIRA F，CAO L X，WANG I，et al．Apoptosis signal-regulating kinase 1 inhibition attenuates cardiac hypertrophy and cardiorenal fibrosis induced by uremic toxins：implications for cardiorenal syndrome［J］．PLoS One，2017，12（11）：e0187459．DOI：10.1371/journal.pone.0187459.
［40］KOH A，DE VADDER F，KOVATCHEVA-DATCHARY P，et al．
From dietary fiber to host physiology：short-chain fatty acids as key bacterial metabolites［J］．Cell，2016，165（6）：1332-1345．DOI：10.1016/j.cell.2016.05.041.
［41］SCHNEEBERGER M，EVERARD A，GóMEZ-VALADéS A G，et al．Akkermansia muciniphila inversely correlates with the onset of inflammation，altered adipose tissue metabolism and metabolic disorders during obesity in mice［J］．Sci Rep，2015，5：16643．DOI：10.1038/srep16643.
［42］KELLY C J，ZHENG L，CAMPBELL E L，et al．Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function［J］．Cell Host Microbe，2015，17（5）：662-671．DOI：10.1016/j.chom.2015.03.005.
［43］CHANG P V，HAO L M，OFFERMANNS S，et al．The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition［J］．Proc Natl Acad Sci USA，2014，111（6）：2247-2252．DOI：10.1073/pnas.1322269111.
［44］WANG H，HOU L，KWAK D，et al．Increasing regulatory T cells with interleukin-2 and interleukin-2 antibody complexes attenuates lung inflammation and heart failure progression［J］．Hypertension，2016，68（1）：114-122．DOI：10.1161/HYPERTENSIONAHA.116.07084.
［45］KN?LL R，LINKE W A，ZOU P J，et al．Telethonin deficiency is associated with maladaptation to biomechanical stress in the mammalian heart［J］．Circ Res，2011，109（7）：758-769．DOI：10.1161/CIRCRESAHA.111.245787.
［46］KOSKIVIRTA I，KASSIRI Z，RAHKONEN O，et al．Mice with tissue inhibitor of metalloproteinases 4（Timp4）deletion succumb to induced myocardial infarction but not to cardiac pressure overload［J］．J Biol Chem，2010，285（32）：24487-24493．DOI：10.1074/jbc.M110.136820.
［47］MARQUES F Z，NELSON E，CHU P Y，et al．High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice［J］．Circulation，2017，135（10）：964-977．DOI：10.1161/CIRCULATIONAHA.116.024545.
［48］HO L C，SUNG J M，SHEN Y T，et al．Egr-1 deficiency protects from renal inflammation and fibrosis［J］．J Mol Med，2016，94（8）：933-942．DOI：10.1007/s00109-016-1403-6.
［49］AMADOR C A，BARRIENTOS V，PE?A J，et al．Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes［J］．Hypertension，2014，63（4）：797-803．DOI：10.1161/HYPERTENSIONAHA.113.02883.
［50］ROTHSCHILD D，WEISSBROD O，BARKAN E，et al．Environment dominates over host genetics in shaping human gut microbiota［J］．Nature，2018，555（7695）：210-215．DOI：10.1038/nature25973.
［51］BIDULESCU A，CHAMBLESS L E，SIEGA-RIZ A M，et al．Usual choline and betaine dietary intake and incident coronary heart disease：the Atherosclerosis Risk in Communities（ARIC）study［J］．BMC Cardiovasc Disord，2007，7（1）：20．DOI：10.1186/1471-2261-7-20.
［52］NAGATA C，WADA K，TAMURA T，et al．Choline and betaine intakes are not associated with cardiovascular disease mortality risk in japanese men and women［J］．J Nutr，2015，145（8）：1787-1792．DOI：10.3945/jn.114.209296.
［53］HEIANZA Y，MA W J，MANSON J E，et al．Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death：a systematic review and meta-analysis of prospective studies［J］．J Am Heart Assoc，2017，6（7）：e004947．DOI：10.1161/JAHA.116.004947.
［54］CONRAADS V M，JORENS P G，DE CLERCK L S，et al．Selective intestinal decontamination in advanced chronic heart failure：a pilot trial［J］．Eur J Heart Fail，2004，6（4）：483-491．DOI：10.1016/j.ejheart.2003.12.004.
［55］MAYERHOFER C C K，AWOYEMI A O，MOSCAVITCH S D，et al．Design of the GutHeart-targeting gut microbiota to treat heart failure-trial：a phaseⅡ，randomized clinical trial［J］．ESC Heart Fail，2018，5（5）：977-984．DOI：10.1002/ehf2.12332.
［56］LIN P P，HSIEH Y M，KUO W W，et al．Probiotic-fermented purple sweet potato yogurt activates compensatory IGF?IR/PI3K/Akt survival pathways and attenuates cardiac apoptosis in the hearts of spontaneously hypertensive rats［J］．Int J Mol Med，2013，32（6）：1319-1328．DOI：10.3892/ijmm.2013.1524.
［57］GAN X T，ETTINGER G，HUANG C X，et al．Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat［J］．Circ Heart Fail，2014，7（3）：491-499．DOI：10.1161/CIRCHEARTFAILURE.113.000978.
［58］COSTANZA A C，MOSCAVITCH S D，FARIA NETO H C，et al．
Probiotic therapy with Saccharomyces boulardii for heart failure patients：a randomized，double-blind，placebo-controlled pilot trial［J］．Int J Cardiol，2015，179（12）：348-350．DOI：10.1016/j.ijcard.2014.11.034.
［59］SHEN N T，MAW A，TMANOVA L L，et al．Timely use of probiotics in hospitalized adults prevents clostridium difficile infection：a systematic review with meta-regression analysis［J］．Gastroenterology，2017，152（8）：1889-1900.e9．DOI：10.1053/j.gastro.2017.02.003.
［60］NICOLUCCI A C，HUME M P，MARTíNEZ I，et al．Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity［J］．Gastroenterology，2017，153（3）：711-722．DOI：10.1053/j.gastro.2017.05.055.
［61］CANI P D，POSSEMIERS S，VAN DE WIELE T，et al．Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability［J］．Gut，2009，58（8）：1091-1103．DOI：10.1136/gut.2008.165886.
［62］CANI P D，NEYRINCK A M，FAVA F，et al．Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia［J］．Diabetologia，2007，50（11）：2374-2383．DOI：10.1007/s00125-007-0791-0.
［63］DEWULF E M，CANI P D，CLAUS S P，et al．Insight into the prebiotic concept：lessons from an exploratory，double blind intervention study with inulin-type fructans in obese women［J］．Gut，2013，62（8）：1112-1121．DOI：10.1136/gutjnl-2012-303304.
［64］LEKAWANVIJIT S，KOMPA A R，MANABE M，et al．Chronic kidney disease-induced cardiac fibrosis is ameliorated by reducing circulating levels of a non-dialysable uremic toxin，indoxyl sulfate［J］．PLoS One，2012，7（7）：e41281．DOI：10.1371/journal.pone.0041281.
［65］WANG Z N，ROBERTS A B，BUFFA J A，et al．Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis［J］．Cell，2015，163（7）：1585-1595．DOI：10.1016/j.cell.2015.11.055.
［66］DE LA CUESTA-ZULUAGA J，MUELLER N T，áLVAREZ-QUINTERO R，et al．Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis，obesity，hypertension and cardiometabolic disease risk factors［J］．Nutrients，2018，11（1）：E51．DOI：10.3390/nu11010051.
［67］TANG T W H，CHEN H C，CHEN C Y，et al．Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair［J］．Circulation，2019，139（5）：647-659．DOI：10.1161/CIRCULATIONAHA.118.035235.
［68］MARQUES F Z，MACKAY C R，KAYE D M.Beyond gut feelings：how the gut microbiota regulates blood pressure［J］．Nat Rev Cardiol，2018，15（1）：20-32．DOI：10.1038/nrcardio.2017.120.
［69］BROWN J M，HAZEN S L.Microbial modulation of cardiovascular disease［J］．Nat Rev Microbiol，2018，16（3）：171-181．DOI：10.1038/nrmicro.2017.149.

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